Qun Li1, Yangli Jin2, Zhisen Shen1, Huigao Liu3, Yi Shen1, Zhenhua Wu1. 1. Department of Otorhinolaryngology Head and Neck Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, People's Republic of China. 2. Department of Doppler Ultrasonic, Ningbo Yinzhou No.2 Hospital, Ningbo, Zhejiang, People's Republic of China. 3. Department of Otorhinolaryngology Head and Neck Surgery, Ningbo Zhenhai Longsai Hospital, Ningbo, Zhejiang, People's Republic of China.
Abstract
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant cancers, and few studies have demonstrated the value of ferroptosis-related genes in prognosis. METHODS: The original counts of RNA sequencing data and clinicopathological data were obtained from TCGA and GSE65858 datasets. Common ferroptosis-related genes related to prognosis were identified from the training set and were included in LASSO to determine the best prognosis. To evaluate the efficacy, time-dependent ROC and Kaplan-Meier (KM) survival analyses were applied. Moreover, univariate and multivariate Cox regression analyses were used to screen independent parameters of prognosis and build a nomogram. Eventually, possible biological pathways were proposed based on GSEA. RESULTS: Among 242 ferroptosis-related genes, we identified that the FLT3, IL6, Keap1, NQO1, SOCS1 and TRIB3 genes were significantly connected with HNSCC patient prognosis as a six-gene signature. After, the patients were divided into high- and low-risk groups based on the six-gene signature. The KM survival curves demonstrated that the high-risk group had worse OS (p < 0.0001) and higher AUC values (0.654, 0.735, and 0.679 for 1-, 3-, and 5-year survival, respectively) for the prognostic signature of the six genes compared with other genes, which were also validated in the GSE65858 dataset. Moreover, GSEA suggested that the epithelial mesenchymal transition pathway was abundant and that the mesenchymal status in the high-risk group was substantially higher than that in the low-risk group. Finally, the immune microenvironment and differences in the content of immune cell types were demonstrated. CONCLUSION: We established a six-ferroptosis-related-gene model crossing clinical prognostic parameters that can predict HNSCC patient prognosis and provide a reliable prognostic evaluation tool to assist clinical treatment decisions.
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant cancers, and few studies have demonstrated the value of ferroptosis-related genes in prognosis. METHODS: The original counts of RNA sequencing data and clinicopathological data were obtained from TCGA and GSE65858 datasets. Common ferroptosis-related genes related to prognosis were identified from the training set and were included in LASSO to determine the best prognosis. To evaluate the efficacy, time-dependent ROC and Kaplan-Meier (KM) survival analyses were applied. Moreover, univariate and multivariate Cox regression analyses were used to screen independent parameters of prognosis and build a nomogram. Eventually, possible biological pathways were proposed based on GSEA. RESULTS: Among 242 ferroptosis-related genes, we identified that the FLT3, IL6, Keap1, NQO1, SOCS1 and TRIB3 genes were significantly connected with HNSCC patient prognosis as a six-gene signature. After, the patients were divided into high- and low-risk groups based on the six-gene signature. The KM survival curves demonstrated that the high-risk group had worse OS (p < 0.0001) and higher AUC values (0.654, 0.735, and 0.679 for 1-, 3-, and 5-year survival, respectively) for the prognostic signature of the six genes compared with other genes, which were also validated in the GSE65858 dataset. Moreover, GSEA suggested that the epithelial mesenchymal transition pathway was abundant and that the mesenchymal status in the high-risk group was substantially higher than that in the low-risk group. Finally, the immune microenvironment and differences in the content of immune cell types were demonstrated. CONCLUSION: We established a six-ferroptosis-related-gene model crossing clinical prognostic parameters that can predict HNSCC patient prognosis and provide a reliable prognostic evaluation tool to assist clinical treatment decisions.
Authors: Joseph H Taube; Jason I Herschkowitz; Kakajan Komurov; Alicia Y Zhou; Supriya Gupta; Jing Yang; Kimberly Hartwell; Tamer T Onder; Piyush B Gupta; Kurt W Evans; Brett G Hollier; Prahlad T Ram; Eric S Lander; Jeffrey M Rosen; Robert A Weinberg; Sendurai A Mani Journal: Proc Natl Acad Sci U S A Date: 2010-08-16 Impact factor: 11.205
Authors: Lauren Averett Byers; Lixia Diao; Jing Wang; Pierre Saintigny; Luc Girard; Michael Peyton; Li Shen; Youhong Fan; Uma Giri; Praveen K Tumula; Monique B Nilsson; Jayanthi Gudikote; Hai Tran; Robert J G Cardnell; David J Bearss; Steven L Warner; Jason M Foulks; Steven B Kanner; Varsha Gandhi; Nancy Krett; Steven T Rosen; Edward S Kim; Roy S Herbst; George R Blumenschein; J Jack Lee; Scott M Lippman; K Kian Ang; Gordon B Mills; Waun K Hong; John N Weinstein; Ignacio I Wistuba; Kevin R Coombes; John D Minna; John V Heymach Journal: Clin Cancer Res Date: 2012-10-22 Impact factor: 12.531